European patent application, EP-176,034-A discloses tetrahydronaphthalene compounds having an ethynylbenzoic group. U.S. Pat. No. 4,739,098 discloses compounds wherein three olefinic units from the acid-containing moiety of retinoic acid are replaced by an ethynylphenyl functionality. These compounds have retinoic acid-like biological activity.
U.S. Pat. No. 4,810,804 (issued on Mar. 7, 1989) based on an application of the same inventor and assigned to the same assignee as the present application, discloses such disubstituted acetylene compounds wherein one of the substituents of the acetylene (ethyne) group is a substituted phenyl group, and the second substituent is a substituted or unsubstituted chromanyl, thiochromanyl, or tetrahydroquinolinyl group. The compounds disclosed and claimed in U.S. Pat. No. 4,810,804 have retinoic acid-like biological activity.
Several U.S. patents issued to the same inventor and assigned to the same assignee as the present application disclose such disubstituted compounds wherein one of the groups is chroman, thiochroman or tetrahydroquinoline and the other is phenyl or pyridyl or another heterocycle. U.S. Pat. No. 5,089,509 describes chroman or thiochroman acetylene derivatives which have a pyridyl group as the other substituent. U.S. Pat. No. 5,234,926 discloses tetrahydroquinolin-ethynyl groups substituted by a monoheterocyclic group such as pyridine. U.S. Pat. No. 5,162,546 discloses (thio)chromanyl-ethynyl groups substituted by phenyl moieties. These three patents are hereby incorporated by reference in their entireties.
Retinoic acid-like activity has been generally recognized in the art to be associated with useful biological activity. Specifically, compounds having retinoic acid-like activity are useful as regulators of cell proliferation, and particularly as agents for treating dermatoses, such as ache, Darier's disease, psoriasis, icthyosis, eczema, atopic dermatitis and epithelial cancers, for treating arthritic diseases and other immunological disorders (e.g. lupus erythematosus) for promoting wound healing, for treating dry eye syndrome and for reversing the effects of sun damage to skin.
With respect to the synthetic processes of the present invention that involve the formation of compounds which are useful for coupling with an acetylenic (ethynyl) function to form the retinoid compounds disclosed in certain of the above cited Chandraratna patents, U.S. Pat. Nos. 5,023,341, 5,053,523 and 5,248,777 disclose processes and compounds useful for coupling to the intermediates prepared according to the process of the present invention and are hereby incorporated by reference in their entireties.